Integrating High-Throughput Sequence Data to Identify Genes and Mechanisms in Optic Nerve Degeneration

Monday, July 20, 2015 - 2:00pm
Fung Auditorium, Powell-Focht Bioengineering Hall
Terry Gaasterland, Ph.D.

Professor of Computational Biology and Genomics
Director, Scripps Genome Center

Integrating High-Throughput Sequence Data to Identify Genes and Mechanisms in Optic Nerve Degeneration


In glaucoma, progressive optic nerve degeneration can lead to irreversible vision impairment and eventual blindness, despite treatment. Genetic causes and influences are not yet clear in primary open angle glaucoma (POAG), the most prevalent form of the disease in North America, Europe, and several other parts of the world. The genetics of POAG are complex; to date, no single causative genomic variant has been established as causing the disease. Genome-wide sequencing of exons from protein coding and non-coding genes in 333 patients with primary open angle glaucoma revealed over 100 associated SNP sites in over 70 genes. To rank and prioritize genes and generate hypotheses about molecular mechanisms disrupted by associated variant sites, mRNA and small RNA (microRNA) were sequenced from ocular tissues relevant to the disease. Analysis protocols and techniques for integrated data interpretation to construct putative regulatory networks underlying disease will be discussed. The approach revealed two strong candidate models explaining neurodegeneration in POAG. Data collection and analysis methods are generally applicable beyond glaucoma to other chronic, progressive diseases associated with aging.


Dr. Terry Gaasterland is a computational molecular biologist trained as a computer scientist. She earned her undergraduate degree in Computer Science and Russian with a minor in Chemistry from Duke University as an A.B. Duke Scholar, and her Ph.D. in Computer Science from University of Maryland. As an Enrico Fermi Fellow at the Department of Energy's Argonne National Laboratory and then as an Assistant Professor of Computer Science at the University of Chicago, she applied techniques from her work in "cooperative answering", natural language processing, and deductive database research to the interpretation of the first three DOE-funded microbial genomes and a fourth Canadian-funded archaeal genome. During seven years as a Head of Lab at Rockefeller University, Dr. Gaasterland focused on the integration of gene expression data and genome sequence data analysis in human and model eukaryotic organisms. Ten years ago, Dr. Gaasterland moved her Laboratory of Computational Genomics to UCSD to establish the Scripps Genome Center, a UCSD resource based at the Scripps Institution of Oceanography in the Marine Biology Division, with bioinformatics hardware and software housed at the San Diego Supercomputer Center. At UCSD, she is now Professor of Computational Biology and Genomics at SIO and a faculty member in UCSD’s Institute for Genomic Medicine. Since receiving the Presidential Early Career Award in Science and Engineering (PECASE) in 2000, she has been continuously funded by the National Science Foundation and the National Institutes of Health to develop and use methods in computational genomics. Her accomplishments in computational molecular biology as well as her early career work in deductive databases is reflected in over 90 refereed publications, with over 80 indexed in PubMed. A member of the NEIGHBOR Consortium to study primary open angle glaucoma (POAG) and the NHGRI Medical Sequencing program, Dr. Gaasterland is sequencing and analyzing variation in transcribed exons genome-wide for 400 primary open angle glaucoma cases and controls. Her work aims to address the general question of how regulation of transcription and translation modulate and affect cell state changes.